Expression of truncated or nonsense proteins play a role or are the causative agent in many inherited disorders and cancers. These truncated or nonsense proteins result from mutations or aberrant mRNA splicing that result in early termination signals in the mRNA. Mammalian Staufen1 (Stau1) is an RNA binding protein that binds to extensive RNA secondary structures, primarily through one or more double-stranded RNA-binding domains. In mammals, the Stau1 gene is ubiquitously expressed and is involved in mRNA transport and translational control. Stau1 is associated with degradation of translationally active mRNAs that bind the double-stranded (ds)RNA binding protein STAU1, a process known as Stua1-mediated mRNA decay or SMD. What is needed or methods of identifying targets for SMD and compositions that can modulate SMD so that disorders associated with early termination signal in mRNA can be properly identified and treated.